WO2013018929A1 - Composé hétérocyclique contenant de l'azote - Google Patents

Composé hétérocyclique contenant de l'azote Download PDF

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WO2013018929A1
WO2013018929A1 PCT/JP2012/070410 JP2012070410W WO2013018929A1 WO 2013018929 A1 WO2013018929 A1 WO 2013018929A1 JP 2012070410 W JP2012070410 W JP 2012070410W WO 2013018929 A1 WO2013018929 A1 WO 2013018929A1
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group
optionally substituted
substituent
compound
optionally
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PCT/JP2012/070410
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English (en)
Inventor
Shigemitsu Matsumoto
Koji Ono
Yusuke Tominari
Taisuke KATOH
Kazuhiro Miwa
Atsushi Hasuoka
Shinichi Imamura
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Takeda Pharmaceutical Company Limited
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Publication of WO2013018929A1 publication Critical patent/WO2013018929A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof

Definitions

  • the present invention relates to a novel compound having a superior activity as an estrogen-related receptor-ct (in the present specification, sometimes to be abbreviated as ERR-a) modulator and useful as an agent for the prophylaxis or
  • ERR-a associated diseases such as malignant tumor (e.g., breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, endometrial carcinoma) and the like.
  • malignant tumor e.g., breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, endometrial carcinoma
  • Nuclear receptors are transcription regulators that respond to various stimuli such as physiological factors (e.g., development and differentiation) , environmental factors and the like, and regulate gene expression in a ligand dependent manner. They form a gene superfamily based on their structural characteristics. Among them are included classic nuclear receptors such as estrogen receptor (ER) with estrogen as a ligand, and the like, and orphan nuclear receptors whose
  • Estrogen-related receptor-a belongs to the estrogen-related receptor subfamily (ERR subfamily)
  • ERR- ⁇ and ERR- ⁇ have additionally been identified as the members of the ERR subfamily, and all the members show high homology with ER in the DNA-binding domain.
  • ER and the ERR subfamily are known to have common target genes such as estrogen-responsive genes and the like.
  • Crosstalks occur between the signal transduction pathways of ER and the ERR subfamily (non-patent documents 1 to 4) .
  • a compound capable of modulating the activity of ERR- ⁇ could provide a therapeutic etfect for both the diseases related to ERR-a and the diseases related to ER, through a direct modulation of the ERR-a transcriptional effect or an indirect effect on the ER signal transduction pathway.
  • an ERR-a modulator is expected to be useful for the prophylaxis or treatment of various disease conditions (e.g., cancers such as breast cancer and the like, diabetes, hyperlipidemia, obesity, metabolic syndrome, arthritis, atherosclerosis, rheumatoid arthritis, atopic dermatitis, osteoporosis, anxiety, depression, Parkinson's disease, Alzheimer's disease etc.) (patent cancers such as breast cancer and the like, diabetes, hyperlipidemia, obesity, metabolic syndrome, arthritis, atherosclerosis, rheumatoid arthritis, atopic dermatitis, osteoporosis, anxiety, depression, Parkinson's disease, Alzheimer's disease etc.) (patent
  • A is a group represented by the formula
  • R 1 , R 2 and R 3 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a heterocyclic group optionally having substituent (s) , an acyl group, or a hydroxyl group optionally substituted by an alkyl group optionally having substituent (s) ;
  • Y is -0-, -S- or -NR a - wherein R a is a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a
  • heterocyclic group optionally having substituent (s ) , an acyl group, or a hydroxyl group optionally substituted by an alkyl group optionally having substituent (s) ;
  • hydrocarbon group optionally having substituent ( s) , a
  • heterocyclic group optionally having substituent (s) , an acyl group, or a hydroxyl group optionally substituted by an alkyl group optionally having substituent (s) ;
  • Y 1 is -0-, -S- or -NR C - wherein R c is a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a
  • heterocyclic group optionally having substituent (s) , or an acyl group;
  • Z 1 is -OR d , -SR d or -NHR d wherein R d are each independently a hydrogen atom, a hydrocarbon group optionally having
  • substituent (s) a heterocyclic group optionally having substituent ( s) , or an acyl group
  • R 4 is a hydrogen atom or an alkyl group optionally navmg substituent (s) ;
  • R 5 , R 6 , R 7 and R 8 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) , an amino group optionally having substituent (s) , a hydroxyl group optionally having a substituent, a thiol group optionally having a substituent, a carbamoyl group optionally having substituent ( s) , an alkyloxycarbonyl group optionally having substituent (s) , a halogen atom, a cyano group or a nitro group;
  • n are each independently an integer of 0 to 3;
  • X is -0-, -CO-, -0-C0-, -C0-0-, -S0 2 -, -SO-, -S-, -S0 2 -0-, -
  • R cl and R c2 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent ( s) , a heterocyclic group optionally having substituent (s ) , an acyl group, or a hydroxyl group optionally substituted by an alkyl group optionally having substituent (s) ; and
  • R 9 is an aromatic ring group optionally having substituent (s) , provided that the following two compound:
  • patent document 4 JP-A-9-3067 ) discloses a compound represented by the formula:
  • Ri is a hydrogen atom, a lower alkyl group, or an unsubstituted or substituted phenyl group,
  • R 2 is an unsubstituted or substituted phenyl group, a pyridyl group, or a 2-benzimidazolyl group having a lower alkyl group, a lower alkoxyalkyl group or an unsubstituted or substituted aralkyl group at N-position,
  • n is an integer of 0 or 1
  • n is an integer of 0 to 3
  • Y is >S, >NH or >N-CH 3 .
  • patent document 5 discloses a compound represented by the formula:
  • R 1 is a hydrogen atom, lower alkyl, optionally substituted aryl, aryl fused to a non-aromatic hydrocarbon ring or a non- aromatic heterocycle, optionally substituted aralkyl,
  • Z is -S-, -SO-, -0-, -OCH 2 -, -CONH-, -C0NHCH 2 -, -N(R 16 )- wherein R 16 is a hydrogen atom, alkyl or aralkyl, or a single bond;
  • X 2 is optionally substituted arylene, optionally substituted heteroarylene, heterocyclediyl, -C ⁇ C- or a single bond;
  • X 3 is alkylene, alkenylene or a single bond
  • A, B, and' E are each independently an oxygen atom or a sulfur atom
  • D is a hydrogen atom or hydroxy lower alkyl
  • Y 1 is -(CH 2 ) m C0-, -(CH 2 ) m C0NH-, - (CH 2 ) m CSNH-, -(CH 2 ) m S0 2 -, -
  • n is an integer of 0 to 3;
  • n is an integer of 1 to 3;
  • Y 2 is a group represented by the formula:
  • R 2 and R 3 are both hydrogen atoms, or
  • the one is optionally substituted aryl, optionally
  • R 4 , R 5 , G ring, J ring and L ring are each independently optionally substituted aryl, optionally substituted
  • heteroaryl optionally substituted cycloalkyl, or
  • broken line ( ) shows presence or absence of a bond
  • p is an integer of 0 to 2
  • broken line ( ) shows presence or absence of a bond
  • a wavy line ( ⁇ ) means that the bond of D is cis or trans relation to E
  • Non-patent document 8 (Chemical & Pharmaceutical Bulletin, 2009, vol.57 (12), p.1415-1420) discloses synthetic route for a compound having the following formula
  • non-patent document 9 (Chemical & Pharmaceutical Bulletin, 2010, vol.58 (8), p.1123-1126) discloses antibacterial activity of the compound.
  • patent document 3 WO 2011/016501 patent document 4: JP-A-9-3067
  • non-patent document 1 J. Clin. Endocrinol. Metab., 2005, vol.90, p.3115-21
  • non-patent document 2 EMBO J., 1999, vol.18, p.4270-9
  • non-patent document 3 Mol . Cell Endocrinol., 2001, vol.172, p.223-33
  • non-patent document 4 J. Biol. Chem. , 1996, vol.271, p.5795- 804
  • non-patent document 5 Circulation, 2004, vol.109, p.433-8
  • non-patent document 6 Cancer Research, 2008, vol.68, p.8805- 12
  • non-patent document 7 Mol. Cancer Ther., 2009, vol.8, p.672- 81
  • non-patent document 8 Chemical & Pharmaceutical Bulletin, 2009, vol.57(12), p.1415-1420
  • non-patent document 9 Chemical & Pharmaceutical Bulletin, 2010, vol.58(8), p.1123-1126
  • colorectal cancer lung cancer, ovarian cancer, endometrial carcinoma
  • lung cancer ovarian cancer, endometrial carcinoma
  • the present inventors have conducted intensive studies in an attempt to solve the above-mentioned problem and found that the following compound represented by the formula (I) or a salt thereof has a superior activity as an ERR-oc modulator, and conducted further studies, which resulted in the
  • the present invention is as follows;
  • A is a cyclic group optionally having substituent (s) ;
  • L a is a bond, -0-, -CO-, -S-, -SO-, -S0 2 ⁇ , -NR L1 - or -NR L1 -C0-;
  • L b is a bond or a Ci_ 3 alkylene group optionally having
  • L c is a bond, -CO-, -0-CO-, -NR L2 -CO-, -S0 2 - or -NR L2 -S0 2 -;
  • R L1 and R L2 are each independently a hydrogen atom, a
  • hydrocarbon group optionally having substituent (s) , a
  • heterocyclic group optionally having substituent (s) , a hydroxy group optionally having a substituent, an amino group
  • ring G is a 4- to 10-membered saturated heterocycle containing one nitrogen atom as a ring-constituting hetero atom, which is optionally bridged and optionally has substituent (s) ; and E is a group represented by the formula
  • X is -S-, -0- or -NR X -; and R 1 , R 2 , R 3 and R x are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a heterocyclic group optionally having substituent ( s ) , a hydroxy group optionally having a substituent, an amino group optionally having substituent (s) , or an acyl group, or
  • R 1 and R 2 in combination optionally form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent (s) , or
  • R 1 and R 3 in combination optionally form, together with the- adjacent nitrogen atoms, a 5- to 7-membered nitrogen- containing heterocycle optionally having substituent (s) , or a salt thereof.
  • A is a cyclic group optionally having substituent (s) ;
  • L a is a bond, -0-, -CO-, -S-, -SO-, -S0 2 ⁇ , -NR L1 - or -NR L1 -CO-;
  • L b is a bond or a Ci_ 3 alkylene group optionally having
  • L c is a bond, -CO-, -0-CO-, -NR L2 -C0-, -S0 2 - or -NR L2 -S0 2 -;
  • R L1 and R L2 are each independently a hydrogen atom, a
  • hydrocarbon group optionally having substituent (s) , a
  • heterocyclic group optionally having substituent (s) , a hydroxy group optionally having a substituent, an amino group
  • ring G is a 4- to 10-membered saturated heterocycle containing one nitrogen atom as a ring-constituting hetero atom, which is optionally bridged and optionally has substituent (s) ; and E is a group represented by the formula [0032]
  • X is -S-, -0- or -NR X -;
  • R 1 , R 2 , R 3 and R x are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a heterocyclic, group optionally having substituent (s) , a hydroxy group optionally having a substituent, an amino group optionally having substituent (s) , or an acyl group, or
  • R 1 and R 2 in combination optionally form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent (s) ,
  • Ci_ 6 alkoxy group optionally substituted by 1 to 3 halogen atoms
  • [4A] The compound or salt of any one of the above-mentioned [1]-[3A], wherein A is a phenyl group, a naphthyl group, a benzofuryl group, an indolyl group, a benzimidazolyl group or a C3-10. cycloalkyl group, each optionally substituted by 1 to 3 substituents selected from
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkoxy group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • Ci_6 alkoxy group optionally substituted by 1 to 3 halogen atoms
  • L a is a bond
  • L b is a bond or a C1-3 alkylene group optionally substituted by 1 to 3 Ci-6 alkyl groups;
  • L c is a bond or -CO-.
  • L a is a bond
  • L b is a Ci-3 alkylene group optionally substituted by 1 to 3 Ci-6 alkyl groups
  • L c is a bond
  • L a is a bond
  • L b is methylene group
  • L c is a bond
  • ring G is an azetidine ring, a pyrrolidine ring, a piperidine ring, an azepane ring, a 3- azabicyclo [3.1.0] hexane ring, a 8-azabicyclo [3.2.1] octane ring, a 3-azabicyclo [3.3.1] nonane ring or a 3- azabicyclo [3.3.0] octane ring, each optionally having
  • ring G is an azetidine ring, a pyrrolidine ring, a piperidine ring, an azepane ring, a 3- azabicyclo [3.1.0] hexane ring, a 8-azabicyclo [3.2.1] octane ring, a 3-azabicyclo [3.3.1] nonane ring or a 3- azabicyclo [3.3.0] octane ring, each optionally substituted by to 3 Ci-6 alkyl groups or one oxo group.
  • X is -S-, -0- or -NR X - ;
  • R x is a Ci-6 alkyl group
  • Ci-6 alkyl group optionally substituted by 1 to 5
  • an amino group optionally mono- or di-substituted by is alkyl group (s) optionally substituted by 1 to 3 hydroxy groups,
  • Ci-6 alkoxy group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a Ci-e alkoxy group and a mono- or di-Ci-6 alkylamino group,
  • Ci- 6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a Ci ⁇ 6 alkoxy group, (ii) a C3-10 cycloalkyl group, and
  • Ci-6 alkyl group optionally substituted by 1 to 3 hydroxy groups
  • Ci-6 alkyl group optionally substituted by 1 to 3 hydroxy groups
  • R 2 is a hydrogen atom
  • R 1 and R 2 in combination form, together with the adjacent nitrogen atom, a 4- to 7-membered nitrogen-containing
  • Ci-6 alkyl group (s) Ci-6 alkyl group (s) .
  • A is a phenyl group, a naphthyl group, a benzofuryl group, an indolyl group, a benzimidazolyl group or a C3-10 cycloalkyl group, each optionally substituted by 1 to 3 substituents selected from
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkoxy group optionally substituted by 1 to 3 halogen atoms
  • L a is a bond
  • L b is a bond or a Ci- 3 alkylene group optionally substituted by 1 to 3 Ci_6 alkyl groups;
  • L c is a bond or -CO-
  • ring G is an azetidine ring, a pyrrolidine ring, a piperidine ring, an azepane ring, a 3-azabicyclo [3.1.0] hexane ring, a 8- azabicyclo [3.2.1] octane ring, a 3-azabicyclo [3.3.1] nonane ring or a 3-azabicyclo [3.3.0] octane ring, each optionally
  • X is -S-, -0- or -NR X -;
  • R x is a Ci_6 alkyl group
  • Ci-6 alkyl group optionally substituted by 1 to 5 substituents selected from
  • R 2 is a hydrogen atom
  • R 1 and R 2 in combination form, together with the adjacent nitrogen atom
  • a pyrrolidine ring optionally substituted by 1 to 3 hydroxy groups or carbamoyl group (s) di-substituted by Ci-6 alkyl groups; or
  • A is a phenyl group optionally substituted by 1 to 3
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • L a is a bond
  • L b is a Ci-3 alkylene group optionally substituted by 1 to 3 Ci_ 6 alkyl groups;
  • L c is a bond
  • ring G is a piperidine ring
  • E is a group represented by the formula [0047]
  • Ci-6 alkyl group optionally substituted by 1 to 5 substituents selected from
  • Ci-6 alkoxy group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a Ci_6 alkoxy group and a di-Ci-6 alkylamino group,
  • Ci-6 alkyl group optionally substituted by 1 to 3 hydroxy groups
  • R 2 is a hydrogen atom; or R 1 and R 2 in combination form, together with the adjacent nitrogen atom,
  • a pyrrolidine ring optionally substituted by 1 to 3 hydroxy groups or carbamoyl grou (s) di-substituted by Ci- 6 alkyl groups; or
  • A is a phenyl group optionally substituted by 1 to 3
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • L is a bond
  • L b is a Ci-3 alkylene group
  • L c is a bond
  • ring G is pyrrolidine ring, a piperidine ring or a 8- azabicyclo [3.2.1] octane ring;
  • E is a group represented by the formula
  • X is -S- or -NR X -;
  • R x is a Ci-6 alkyl group
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from (a) an amino group di-substituted by Ci_ 6 alkyl groups optionally substituted by 1 to 3 hydroxy groups,
  • R 2 is a hydrogen atom.
  • A is a phenyl group optionally substituted by 1 to 3
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • L a is a bond
  • L b is a C1-3 alkylene group
  • L c is a bond
  • ring G is pyrrolidine ring or a piperidine ring
  • E is a group represented by the formula
  • X is -S- or -NR X -;
  • R x is a Ci-6 alkyl group
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from
  • R 2 is a hydrogen atom.
  • A is a phenyl group substituted by 1 to 3 substituents
  • Ci_6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • L a is a bond
  • L b is a Ci-3 alkylene group
  • L° is a bond
  • ring G is a piperidine ring
  • E is a group represented by the formula
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from
  • R 2 is a hydrogen atom.
  • A is a phenyl group substituted by 1 to 3 substituents selected from a Ci_ 6 alkyl group optionally substituted by 1 to 3 halogen atoms;
  • L a is a bond
  • L b is a Ci-3 alkylene group
  • L is a bond
  • ring G is a piperidine ring
  • E is a group represented by the formula
  • R 2 is a hydrogen atom.
  • a medicament comprising the compound or salt of any one of the above-mentioned [1]-[16].
  • a method of inversing ERR-a in a mammal which comprises administering an effective amount of the compound or salt of any one of the above-mentioned [1]-[16] to a mammal.
  • a method for the prophylaxis or treatment of cancer in a mammal which comprises administering an effective amount of the compound or salt of any one of the above-mentioned [1]- [16] to a mammal.
  • [21A] A method for the prophylaxis or treatment of breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer or endometrial carcinoma in a mammal, which comprises administering an effective amount of the compound or salt of any one of the above-mentioned [1]-[16] to a mammal. [0066]
  • [22A] Use of the compound or salt of any one of the above- mentioned [1]-[16] for the production of an agent for the prophylaxis or treatment of breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer or endometrial carcinoma.
  • [23A] The compound or salt of any one of the above-mentioned [1]-[16] for use as an agent for the prophylaxis or treatment of breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer or endometrial carcinoma.
  • the compound of the present invention has a superior activity as an ERR-a modulator (particularly, inverse agonist) and superior properties from the aspect of in vivo kinetics and the like, it is useful as an agent for the prophylaxis or treatment of ERR-a associated diseases such as malignant tumor (e.g., breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, endometrial carcinoma) and the like.
  • malignant tumor e.g., breast cancer, malignant lymphoma, multiple myeloma, prostate cancer, colorectal cancer, lung cancer, ovarian cancer, endometrial carcinoma
  • halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • Ci-6 alkyl group means methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1, 1-dimethylbutyl, 2, 2-dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl and the like .
  • butoxycarbonyl isobutoxycarbonyl, sec-butoxycarbonyl, tert- butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like .
  • Ci-6 alkyl-carbonyl group means acetyl, propanoyl
  • butanoyl 2-methylpropanoyl, pentanoyl, 3-methylbutanoyl, 2- methylbutanoyl, 2, 2-dimethylpropanoyl, hexanoyl, heptanoyl and the like.
  • E is a group represented by the formula
  • R 3 is a hydrogen atom contains a tautomer such
  • the group contains any of the above-mentioned tautomers.
  • Ea may contain any possible tautomer.
  • X is -S-, -0- or -NR X -, and R 1 , R 2 , R 3 and R x are each independently a hydrogen atom, a hydrocarbon group optionally having substituent (s) , a heterocyclic group optionally having substituent (s) , a hydroxy group optionally having a
  • substituent an amino group optionally having substituent (s) , or an acyl group, or R 1 and R 2 in combination optionally form, together with the adjacent nitrogen atom, a nitrogen- containing heterocycle optionally having substituent (s) , or R 1 and R 3 in combination optionally form, together with the
  • Examples of the "hydrocarbon group" of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x include a Ci-io alkyl group, a C 2 -io alkenyl group, a C 2 -io alkynyl group, a C 3 _io cycloalkyl group, a C3-10 cycloalkenyl group, a C 4 _ io cycloalkadienyl group, a C6-14 aryl group, a C 7 _i 3 aralkyl group, a Cs-i3 arylalkenyl group, a C 3 _i 0 cycloalkyl-Ci_ 6 alkyl group and the like.
  • examples of the Ci_ 10 alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1- ethylpropyl, hexyl, isohexyl, 1, 1-dimethylbutyl, 2,2- dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, nonyl, decyl and the like.
  • Examples of the C 2 -io alkenyl group include ethenyl, 1- propenyl, 2-propenyl, 2-methyl-l-propenyl, 1-butenyl, 2- butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3- hexenyl, 5-hexenyl, 1-heptenyl, 1-octenyl and the like.
  • Examples of the C 2 -io alkynyl group include ethynyl, 1- propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1- pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2- hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 4-methyl-2-pentynyl , 1-heptynyl, 1-octynyl and the like.
  • Examples of the C 3 _i 0 cycloalkyl group include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2.2.1] heptyl, bicyclo [2.2.2 ] octyl, bicyclo [ 3.2.1] octyl, bicyclo[3.2.2]nonyl, bicyclo [3.3.1] nonyl, bicyclo [4.2.1] nonyl, bicyclo [4.3.1] decyl, adamantyl and the like.
  • Examples of the C 3 -i 0 cycloalkenyl group include 2- cyclopenten-l-yl, 3-cyclopenten-l-yl, 2-cyclohexen-l-yl, 3- cyclohexen-l-yl and the like.
  • Examples of the C -10 cycloalkadienyl group include 2,4- cyclopentadien-l-yl, 2, -cyclohexadien-l-yl, 2,5- cyclohexadien-l-yl and the like.
  • cycloalkenyl group and C4-10 cycloalkadienyl group each may be fused with a benzene ring, and examples of such fused ring group include indanyl, dihydronaphthyl, tetrahydronaphthyl, fluorenyl and the like.
  • Examples of the C6-1 aryl group include phenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, biphenylyl and the like.
  • Examples of the C 7 _i 3 aralkyl group include benzyl,
  • Examples of the Cs- arylalkenyl group include styryl and the like.
  • Examples of the C3-10 cycloalkyl-Ci_ 6 alkyl group include cyclopropylmethyl , cyclohexylmethyl, 1-cyclohexylethyl, 2- cyclohexylethyl and the like.
  • Ci-10 alkyl group, C 2 -io alkenyl group and C 2 -io alkynyl group exemplified as the aforementioned "hydrocarbon group” optionally have 1 to 3 substituents at substitutable
  • a C3-10 cycloalkyl group e.g., cyclopropyl, cyclohexyl
  • substituents selected from
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • an aromatic heterocyclic group e.g., thienyl, furyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, tetrazolyl,
  • oxadiazolyl pyrazinyl, quinolyl, indolyl, pyrimidinyl, imidazolyl, pyrazolyl, thiadiazolyl, isoxazolyl
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom and a hydroxy group
  • a non-aromatic heterocyclic group e.g., tetrahydrofuryl, morpholinyl, thiomorpholinyl, piperidyl, pyrrolidinyl, piperazinyl, dioxolyl, dioxolanyl, 1, 3-dihydro-2-benzofuranyl, thiazolidinyl, tetrahydropyranyl ) optionally substituted by 1 to 3 substituents selected from
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from
  • Ci-6 alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from
  • an aromatic heterocyclic group e.g., thienyl, furyl, pyridyl, oxazolyl, thiazolyl, tetrazolyl,
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms (e.g., trifluoromethyl) , and
  • a C7-13 aralkyl-carbonyl group e.g., benzylcarbonyl, phenethylcarbonyl
  • an aromatic heterocyclyl-carbonyl group e.g., an aromatic heterocyclyl-carbonyl group
  • oxazolylcarbonyl thiazolylcarbonyl , tetrazolylcarbonyl, oxadiazolylcarbonyl, pyrazinylcarbonyl, quinolylcarbonyl, indolylcarbonyl, imidazolylcarbonyl, pyrazolylcarbonyl, thiadiazolylcarbonyl, isoxazolylcarbonyl) optionally
  • an aromatic heterocyclyl-carbamoyl group e.g., an aromatic heterocyclyl-carbamoyl group
  • oxazolylcarbamoyl thiazolylcarbamoyl, tetrazolylcarbamoyl, oxadiazolylcarbamoyl, pyrazinylcarbamoyl, quinolylcarbamoyl, indolylcarbamoyl, imidazolylcarbamoyl, pyrazolylcarbamoyl , thiadiazolylcarbamoyl, isoxazolylcarbamoyl) ,
  • Ci-6 alkyl-carbamoyl group e.g., methylcarbamoyl, ethylcarbamoyl
  • a C 6 -i4 aryl-carbamoyl group e.g., phenylcarbamoyl, 1- naphthylcarbamoyl, 2-naphthylcarbamoyl
  • aryl-carbamoyl group e.g., phenylcarbamoyl, 1- naphthylcarbamoyl, 2-naphthylcarbamoyl
  • a C 7 -i3 aralkyl-carbamoyl group e.g., benzylcarbamoyl
  • a Ci-6 alkylsulfonyl group e.g., methylsulfonyl, ethylsulfonyl, isopropylsulfonyl
  • a Ce-14 arylsulfonyl group e.g., benzenesulfonyl , toluenesulfonyl, 1-naphthalenesulfonyl, 2- naphthalenesulfonyl
  • a Ce-14 arylsulfonyl group e.g., benzenesulfonyl , toluenesulfonyl, 1-naphthalenesulfonyl, 2- naphthalenesulfonyl
  • Ci-6 alkoxy-carbonyl group optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkylsulfonyl group e.g., methylsulfonyl ) optionally substituted by 1 to 3 halogen atoms;
  • Ci-6 alkyl group optionally substituted by 1 to 3 substituents selected from
  • an aromatic heterocyclic group e.g., thienyl, furyl, pyridyl, oxazolyl, thiazolyl, tetrazolyl,
  • an aromatic heterocyclyl-Ci_ 6 alkyl group e.g., an aromatic heterocyclyl-Ci_ 6 alkyl group
  • a thiocarbamoyl group optionally mono- or di-substituted by Ci-6 alkyl groups optionally substituted by 1 to 3 halogen atoms
  • a sulfamoyl group optionally mono- or di-substituted by Ci-6 alkyl groups optionally substituted by 1 to 3 halogen atoms
  • Ci-6 alkoxy group optionally substituted by 1 to 3 substituents selected from
  • a C3-10 cycloalkyloxy group e.g., cyclohexyloxy
  • a C 6 -i4 aryloxy group e.g., phenoxy, naphthyloxy
  • Ci_6 alkyl-carbonyloxy group e.g., acetyloxy, tert- butylcarbonyloxy
  • Ci-6 alkylthio group e.g., methylthio, ethylthio
  • halogen atoms optionally substituted by 1 to 3 halogen atoms
  • a C 6 -i4 arylthio group e.g., phenylthio, naphthylthio
  • Ci-6 alkylsulfinyl group e.g., methylsulfinyl
  • (32) a C3-10 cycloalkyl-Ci-6 alkyloxy group (e.g., cyclopropylmethyloxy) ;
  • a mono or di-Ci-6 alkylphosphoryl group (e.g.,
  • Ci-6 alkyl group optionally substituted by 1 to 3 halogen atoms
  • substituents When the number of substituents is two or more, the substituents may be the same or different.
  • hydrocarbon group optionally have 1 to 3 substituents at substitutable position(s).
  • Ci_6 alkyl group optionally substituted by 1 to 3
  • a non-aromatic heterocycleoxy group e.g., piperidyloxy, tetrahydropyranyloxy
  • an amino group optionally mono- or di-substituted by Ci_ 6 alkyl groups
  • Ci-6 alkyl-carbonyloxy group e.g., acetyloxy, tert- butylcarbonyloxy
  • an aromatic heterocyclic group e.g., thienyl, furyl, pyridyl, oxazolyl, thiazolyl, tetrazolyl, oxadiazolyl, pyrazinyl, quinolyl, indolyl, imidazolyl, pyrazolyl,
  • Ci-6 alkyl groups optionally substituted by 1 to 3 hydroxy groups (e.g., hydroxymethyl) , and
  • a non-aromatic heterocyclic group e.g., piperidyl, tetrahydropyranyl
  • substituents When the number of substituents is two or more, the substituents may be the same or different.
  • heterocyclic group of the “heterocyclic group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x include an aromatic heterocyclic group and a non-aromatic heterocyclic group.
  • examples of the aromatic heterocyclic group include a 4- to 7-membered (preferably 5- or 6-membered) monocyclic aromatic heterocyclic group containing, as a ring-constituting atom besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom, and a fused aromatic heterocyclic group.
  • examples of the fused aromatic heterocyclic group include a group derived from a group
  • monocyclic aromatic heterocyclic group is fused with one or two selected from 5- or 6-membered aromatic heterocycle
  • nitrogen atoms e.g., pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine
  • aromatic heterocycle containing one sulfur atom e.g.,
  • aromatic heterocyclic group examples include
  • monocyclic aromatic heterocyclic groups such as furyl (e.g., 2-furyl, 3-furyl) , thienyl (e.g., 2-thienyl, 3-thienyl) , pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl) , pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl) ,
  • pyridazinyl e.g., 3-pyridazinyl, 4-pyridazinyl
  • pyrazinyl e.g., 2-pyrazinyl
  • pyrrolyl e.g., 2-pyrrolyl, 3-pyrrolyl
  • imidazolyl e.g., 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5- imidazolyl
  • pyrazolyl e.g., 1-pyrazolyl, 3-pyrazolyl, 4- pyrazolyl, 5-pyrazolyl
  • thiazolyl e.g., 2-thiazolyl, 4- thiazolyl, 5-thiazolyl
  • isothiazolyl e.g., 3-isothiazolyl , 4-isothiazolyl, 5-isothiazolyl
  • oxazolyl e.g., 2-oxazolyl, 4-oxazolyl, 5-
  • quinolyl e.g., 2- quinolyl, 3-quinolyl, 4-quinolyl, 6-quinolyl
  • isoquinolyl e.g., isoquinolyl
  • quinazolyl e.g., 2-quinazolyl, 4- quinazolyl
  • quinoxalyl e.g., 2-quinoxalyl, 6-quinoxalyl
  • benzofuranyl e.g., 2-benzofuranyl, 3-benzofuranyl, 4- benzofuranyl , 5-benzofuranyl, 6-benzofuranyl, 7-benzofuranyl
  • benzothienyl e.g., 2-benzothienyl, 3-benzothienyl
  • benzoxazolyl e.g., 2-benzoxazolyl
  • benzisoxazolyl e.g., 7- benzisoxazolyl
  • benzothiazolyl e.g., 2-benzothiazolyl
  • benzimidazolyl e.g., benzimidazol-l-yl, benzimidazol-2-yl, benzimidazol-5-yl
  • benzotriazolyl e.g., 1H-1,2,3- benzotriazol-5-yl
  • benzothiadiazolyl e.g., 1,2,3- benzothiadiazol-5-yl
  • indolyl e.g., indol-l-yl, indol-2-yl, indol-3-yl, indol-5-yl
  • indazolyl e.g., lH-indazol-3-yl
  • non-aromatic heterocyclic group examples include a
  • 3- to 7-membered (preferably 4- to 6-membered) monocyclic non- aromatic heterocyclic group containing, as a ring- constituting atom besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom, and a fused non-aromatic heterocyclic group.
  • the fused non-aromatic heterocyclic group include a group derived from a group wherein a group corresponding to such 4- to 7-membered monocyclic non-aromatic heterocyclic group is fused with one or two selected from a 5- or 6-membered
  • nitrogen atoms e.g., pyrrole, imidazole, pyrazole, pyrazine, pyridine, pyrimidine
  • a 5-membered aromatic or non-aromatic heterocycle containing one sulfur atom e.g., thiophene
  • a benzene ring and the like and the like.
  • non-aromatic heterocyclic group examples include
  • oxiranyl e.g., 2-oxiranyl
  • oxetanyl e.g., 2-oxetanyl, 3- oxetanyl
  • aziridinyl e.g., 1-aziridinyl, 2-aziridinyl
  • azetidinyl e.g., 1-azetidinyl, 2-azetidinyl, 3-azetidinyl
  • pyrrolidinyl e.g., 1-pyrrolidinyl, 2-pyrrolidinyl
  • piperidyl e.g., 1-piperidyl, 2-piperidyl, 3-piperidyl, 4-piperidyl
  • homopiperidyl e.g., 1-homopiperidyl, 2-homopiperidyl, 3- homopiperidyl, 4-homopiperidyl
  • tetrahydropyridyl e.g.,
  • morpholino morpholino
  • thiomorpholinyl e.g., thiomorpholino
  • piperazinyl e.g., 1-piperazinyl, 2-piperazinyl, 3- piperazinyl
  • hexamethyleniminyl e.g., hexamethylenimin-l-yl
  • oxazolidinyl e.g., oxazolidin-2-yl
  • thiazolidinyl e.g., thiazolidin-2-yl
  • imidazolidinyl e.g., imidazolidin-2-yl, imidazolidin-3-yl
  • oxazolinyl e.g., oxazolin-2-yl
  • thiazolinyl e.g., thiazolin-2-yl
  • imidazolinyl e.g.,
  • dihydrooxadiazolyl e.g., 4, 5-dihydro-l, 2, -oxadiazol-3-yl
  • 2-thioxo-l 2-thioxo-l
  • 3-oxazolidin-5-yl pyranyl (e.g., 4-pyranyl)
  • tetrahydropyranyl e.g., 2-tetrahydropyranyl, 3- tetrahydropyranyl, 4-tetrahydropyranyl
  • thiopyranyl e.g., 4- thiopyranyl
  • tetrahydrothiopyranyl e.g., 2- tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl, 4- tetrahydrothiopyranyl
  • 1-oxidotetrahydrothiopyranyl e.g., 1- oxidotetrahydrothiopyran-4-yl
  • 1,1- dioxidotetrahydrothiopyranyl e.g., 1,1- dioxidotetrahydrothiopyran-4-yl
  • tetrahydrofuryl e.g., tetrahydrofuran-3-yl, tetrahydrofuran-2-yl
  • pyrroluryl e.
  • tetrahydropyrimidin-l-yl e.g., 2,3- dihydro-lH-1, 2, 3-triazol-l-yl
  • dihydrotriazolyl e.g., 2,3- dihydro-lH-1, 2, 3-triazol-l-yl
  • tetrahydrotriazolyl e.g., 2,3,4, 5-tetrahydro-lH-l , 2, 3-triazol-l-yl
  • oxodihydrooxadiazolyl e.g., 5-oxo-4, 5-dihydro-l, 2, 4- oxadiazol-3-yl
  • oxodihydrooxadiazolyl e.g., 5-oxo-4, 5-dihydro-l, 2, 4- oxadiazol-3-yl
  • non-aromatic heterocyclic groups such as dihydroindolyl (e.g., 2, 3-dihydro-lH-indol-l-yl) , dihydroisoindolyl (e.g., 1, 3-dihydro-2H-isoindol-2-yl) , dihydrobenzofuranyl (e.g., 2,3- dihydro-l-benzofuran-5-yl) , dihydrobenzodioxinyl (e.g., 2,3- dihydro-1, -benzodioxinyl ) , dihydrobenzodioxepinyl (e.g., 3,4- dihydro-2H-l, 5-benzodioxepinyl) , tetrahydrobenzofuranyl (e.g., 4 , 5, 6, 7-tetrahydro-l-benzofuran-3-yl) , chromenyl (e.g.
  • dihydroquinolinyl e.g., 1 , 2-dihydroquinolin-4-yl
  • tetrahydroquinolinyl e.g., 1, 2, 3, 4-tetrahydroquinolin-4-yl
  • dihydroisoquinolinyl e.g., 1, 2-dihydroisoquinolin-4-yl
  • tetrahydroisoquinolinyl e.g., 1, 2, 3, -tetrahydroisoquinolin- 4-yl, 1, 2, 3, 4-tetrahydroisoquinolin-2-yl
  • dihydrophthalazinyl e.g., 1, 4-dihydrophthalazin-4-yl
  • tetrahydrobenzoazepinyl e.g., 2, 3, 4, 5-tetrahydro-lH-benzo [c] azepin-l-yl
  • tetrahydroquinolinyl e.g., 1, 2, 3, 4-tetrahydroquinolin-4-yl
  • dihydroisoquinolinyl e.g.
  • the aforementioned aromatic heterocyclic group and non- aromatic heterocyclic group optionally have 1 to 3
  • substituent of the aromatic heterocyclic group examples include those exemplified as the substituents that C6-14 aryl and the like exemplified as the hydrocarbon group" of the aforementioned "hydrocarbon group optionally having
  • substituents is two or more, the substituents may be the same or different.
  • heterocyclic group include those exemplified as the
  • substituents may be the same or different.
  • Examples of the "hydroxy group optionally having a substituent" for R 1 , R 2 , R 3 or R x include a hydroxy group
  • substituent ( s ) selected from a Ci_io alkyl group, a C 2 -io alkenyl group, a C 3 _io cycloalkyl group, a C3-10 cycloalkenyl group, a C 6 -i4 aryl group, a C 7 -i 3 aralkyl group, a Cs-13 arylalkenyl group, a C3-10 cycloalkyl-Ci- 6 alkyl group, a C1- 6 alkyl-carbonyl group, a heterocyclic group and the like, each optionally having substituent (s) .
  • substituent ( s ) selected from a Ci_io alkyl group, a C 2 -io alkenyl group, a C 3 _io cycloalkyl group, a C3-10 cycloalkenyl group, a C 6 -i4 aryl group, a C 7 -i 3 aralky
  • Ci-10 alkyl group examples include those exemplified as the "hydrocarbon group" of the "hydrocarbon group optionally having
  • heterocyclic group examples include the aromatic heterocyclic group and non-aromatic heterocyclic group those exemplified as the "heterocyclic group” of the “heterocyclic group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x .
  • hydrocarbon group optionally having substituent (s) for R 1 , R 2 , R 3 or R x optionally have.
  • Examples of the substituent of the C 3 _io cycloalkyl group, C3-10 cycloalkenyl group, C3-10 cycloalkyl-Ci_ 6 alkyl group and non-aromatic heterocyclic group include those exemplified as the substituents that C3-10 cycloalkyl group and the like
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • heterocyclic group include those exemplified as the
  • substituent (s) " for R 1 , R 2 , R 3 or R x include an amino group optionally substituted by 1 or 2 substituents selected from a Ci-10 alkyl group, a C 2 -io alkenyl group, a C3-10 cycloalkyl group, a C3-10 cycloalkenyl group, a C6-14 aryl group, a C 7 -i 3 aralkyl group, a Cs-i3 arylalkenyl group, a C3-10 cycloalkyl-Ci- 6 alkyl group and a heterocyclic group, each optionally having
  • Ci-10 alkyl group examples include those exemplified as the "hydrocarbon group" of the "hydrocarbon group optionally having
  • heterocyclic group examples include the aromatic heterocyclic group and non-aromatic heterocyclic group include those exemplified as the "heterocyclic group" of the
  • heterocyclic group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x .
  • the Ci-10 alkyl group, C 2 -io alkenyl group, C 3 _io cycloalkyl group, C3-10 cycloalkenyl group, Cg- aryl group, C 7 -i 3 aralkyl group, Ce-13 arylalkenyl group, C3-10 cycloalkyl-Ci- S alkyl group, aromatic heterocyclic group and non-aromatic heterocyclic group optionally have 1 to 3 substituents at substitutable position(s). When the number of substituents is two or more, the substituents may be the same or different.
  • Examples of the substituent of the Ci_i 0 alkyl group and C2-10 alkenyl group include those exemplified as the
  • Examples of the substituent of the C3-10 cycloalkyl group, C3-10 cycloalkenyl group, C3-10 cycloalkyl-Ci- 6 alkyl group and non-aromatic heterocyclic group include those exemplified as the substituents that C3-.10 cycloalkyl group and the like exemplified as the "hydrocarbon group" of the "hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • Examples of the substituent of the C 6 -i 4 aryl group, C 7 _i 3 aralkyl group, Ce-13 arylalkenyl group and aromatic heterocyclic group include those exemplified as the substituents that C 6 -i 4 aryl cycloalkyl group and the like exemplified as the
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • Examples of the "acyl group” for R 1 , R 2 , R 3 or R x and the “acyl group” as the substituent of the aforementioned “amino group optionally having substituent (s) " include a group represented by the formula: -COR A , -CO-OR A , -S0 2 R A , -SOR A , -CO- NR A 'R B ', -S0 2 -NR A 'R B ' , -S0 2 -NR A ' (COR B ' ) , -CS-NR A ' R B ' wherein R A is a hydrogen atom, a hydrocarbon group optionally having
  • R A ' is a hydrogen atom, a hydroxy group optionally having a substituent, a hydrocarbon group
  • R B ' is a hydrogen atom, a hydrocarbon group optionally having substituent (s) or a heterocyclic group optionally having substituent (s) ; or R A ' and R B ' in combination form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent (s) .
  • Examples of the "hydrocarbon group optionally having substituent ( s ) " and “heterocyclic group optionally having substituent (s) " for R A , R A ' or R B ' include those similar to the “hydrocarbon group optionally having substituent (s) " and
  • heterocyclic group optionally having substituent ( s ) " for R 1 , R 2 , R 3 or R x .
  • Examples of the "hydroxy group optionally having a substituent" for R A ' include those similar to the "hydroxy group optionally having a substituent" for R 1 , R 2 , R 3 or R x .
  • substituent (s) " formed by R A ' and R B ' in combination together with the adjacent nitrogen atom include a 5- to 7-membered nitrogen-containing heterocycle containing, as a ring- constituting atom besides carbon atom, at least one nitrogen atom, and optionally further containing 1 or 2 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom.
  • the nitrogen-containing heterocycle include pyrrolidine, imidazolidine, pyrazolidine, piperidine, piperazine, morpholine, thiomorpholine,
  • the nitrogen-containing heterocycle optionally has 1 to 3 (preferably 1 or 2) substituents at substitutable position (s).
  • substituents include those exemplified as the substituent that the C 3 _io cycloalkyl group and the like
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • substituents may be the same or different.
  • acyl group examples include
  • Examples of the "C 2 - 6 alkenyl-carbonyl group” of the “C 2 -6 alkenyl-carbonyl group optionally having substituent (s) " include ethenylcarbonyl, 1-propenylcarbonyl, 2- propenylcarbonyl, 2-methyl-l-propenylcarbonyl, 1- butenylcarbonyl, 2-butenylcarbonyl, 3-butenylcarbonyl, 3- methyl-2-butenylcarbonyl, 1-pentenylcarbonyl, 2- pentenylcarbonyl , 3-pentenylcarbonyl, 4-pentenylcarbonyl, 4- methyl-3-pentenylcarbonyl, 1-hexenylcarbonyl, 2- hexenylcarbonyl, 3-hexenylcarbonyl, 4-hexenylcarbonyl, 5- hexenylcarbonyl and the like.
  • Examples of the "C 2 -6 alkynyl-carbonyl group" of the “C 2 - 6 alkynyl-carbonyl group optionally having substituent (s) " include ethynylcarbonyl, 1-propynylcarbonyl, 2- propynylcarbonyl, 1-butynylcarbonyl, 2-butynylcarbonyl, 3- butynylcarbonyl, 1-pentynylcarbonyl, 2-pentynylcarbonyl, 3- pentynylcarbonyl, 4-pentynylcarbonyl, 1-hexynylcarbonyl, 2- hexynylcarbonyl, 3-hexynylcarbonyl, 4-hexynylcarbonyl, 5- hexynylcarbonyl and the like.
  • substituent (s) " include cyclopropylcarbonyl
  • substituent (s) " include 2-cyclopropen-l-ylcarbonyl, 2- cyclobuten-l-ylcarbonyl, 2-cyclopenten-l-ylcarbonyl, 3- cyclopenten-l-ylcarbonyl, 2-cyclohexen-l-ylcarbonyl, 3- cyclohexen-l-ylcarbonyl and the like.
  • Examples of the " ⁇ - ⁇ aryl-carbonyl group" of the “C 6 -io aryl-carbonyl group optionally having substituent (s) " include benzoyl, 1-naphthoyl, 2-naphthoyl and the like.
  • heterocyclylcarbonyl group optionally having substituent ( s ) include (1) 5- or 6-membered monocyclic aromatic heterocycle (e.g., furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyridine, pyrazole etc .
  • 5- or 6-membered monocyclic aromatic heterocycle e.g., furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyridine, pyrazole etc .
  • substituent (s) " include ethenyloxycarbonyl, 1- propenyloxycarbonyl , 2-propenyloxycarbonyl, 1- butenyloxycarbonyl, 2-butenyloxycarbonyl , 3-butenyloxycarbonyl,
  • substituent (s) " include ethynyloxycarbonyl, 1- propynyloxycarbonyl, 2-propynyloxycarbonyl, 1- butynyloxycarbonyl, 2-butynyloxycarbonyl, 3-butynyloxycarbonyl, 1-pentynyloxycarbonyl, 2-pentynyloxycarbonyl, 3- pentynyloxycarbonyl, 4-pentynyloxycarbonyl, 1- hexynyloxycarbonyl, 2-hexynyloxycarbonyl, 3-hexynyloxycarbonyl , 4-hexynyloxycarbonyl, 5-hexynyloxycarbonyl and the like.
  • substituent (s) " include cyclopropyloxycarbonyl
  • Examples of the "C 3 - 6 cycloalkenyloxy-carbonyl group” of the “C3-6 cycloalkenyloxy-carbonyl group optionally having substituent (s) " include 2-cyclopropen-l-yloxycarbonyl, 2- cyclobuten-l-yloxycarbonyl, 2-cyclopenten-l-yloxycarbonyl, 3- cyclopenten-l-yloxycarbonyl, 2-cyclohexen-l-yloxycarbonyl, 3- cyclohexen-l-yloxycarbonyl and the like.
  • Examples of the "C 6 -io aryloxy-carbonyl group" of the “C 6 - 10 aryloxy-carbonyl group optionally having substituent ( s ) " include phenoxycarbonyl, 1-naphthyloxycarbonyl, 2- naphthyloxycarbonyl and the like.
  • substituent (s) include (1) 5- or 6-membered monocyclic
  • aromatic heterocycle e.g., furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyridine,
  • aromatic heterocycle e.g., benzofuran, isobenzofuran,
  • Examples of the "Ci_ 6 alkylsulfonyl group" of the “Ci_ 6 alkylsulfonyl group optionally having substituent (s) " include, unless otherwise specified, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl,
  • Ci-6 alkyl-carbonyl group C 2 -6 alkenyl-carbonyl group
  • heterocyclylcarbonyl group Ci_ 6 alkoxy-carbonyl group, C 2 _ 6 alkenyloxy-carbonyl group, C 2 _ 6 alkynyloxy-carbonyl group, C 3 _ 6 cycloalkyloxy-carbonyl group, C3-6 cycloalkenyloxy-carbonyl group, C 6 -io aryloxy-carbonyl group, heterocyclyloxycarbonyl group and Ci_ 6 alkylsulfonyl group optionally have 1 to 3 substituents at substitutable position (s). When the number of substituents is two or more, the substituents may be the same or different.
  • Examples of the substituent of the Ci- 6 alkyl-carbonyl group, C 2 -6 alkenyl-carbonyl group, C 2 -6 alkynyl-carbonyl group, Ci-6 alkoxy-carbonyl group, C 2 -6 alkenyloxy-carbonyl group, C 2 -6 alkynyloxy-carbonyl group and Ci-6 alkylsulfonyl group include those exemplified as the substituent that the Ci_i 0 alkyl group and the like exemplified as the "hydrocarbon group" of the
  • hydrocarbon group optionally having substituent (s) for R 1 , R 2 , R 3 or R x optionally have.
  • heterocyclylcarbonyl group C 3 - 6 cycloalkyloxy-carbonyl group, C 3 _6 cycloalkenyloxy-carbonyl group and heterocyclyloxycarbonyl group include those exemplified as the substituent that the C 3 _ 10 cycloalkyl group and the like exemplified as the
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have, excluding oxo when the heterocycle of the heterocyclylcarbonyl group and heterocyclyloxycarbonyl group are each an aromatic heterocycle .
  • Examples of the substituent of the C 6 -io aryl-carbonyl group and C 6 -io aryloxy-carbonyl group include those exemplified as the substituent that the C 6 -i4 aryl group and the like
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • substituent (s) " include a carbamoyl group optionally
  • Ci_io alkyl group substituted by 1 or 2 substituents selected from a Ci_io alkyl group, a C 2 -io alkenyl group, a C 3 _i 0 cycloalkyl group, a C 3 -i 0 cycloalkenyl group, a C3-10 cycloalkyl-Ci_ 6 alkyl group, a C 6 -i4 aryl group, a C 7 _i 3 aralkyl group, a C 8 -i3 arylalkenyl group and a heterocyclic group and the like, each optionally having substituent (s) .
  • substituents selected from a Ci_io alkyl group, a C 2 -io alkenyl group, a C 3 _i 0 cycloalkyl group, a C 3 -i 0 cycloalkenyl group, a C3-10 cycloalkyl-Ci_ 6 alkyl group,
  • Ci-10 alkyl group examples include C 2 -io alkenyl group, C3-10 cycloalkyl group, C3-10 cycloalkenyl group, C3-10 cycloalkyl-Ci-6 alkyl group, C 6 -i4 aryl group, C 7 - 13 aralkyl group, and C 8 -i3
  • arylalkenyl group include those exemplified as the
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x .
  • heterocyclic group examples include the aromatic heterocyclic group and non-aromatic heterocyclic group those exemplified as the "heterocyclic group” of the “heterocyclic group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x .
  • Examples of the substituent of the Ci-io alkyl group and C 2 -io alkenyl group include those exemplified as the
  • Examples of the substituent of the C3-10 cycloalkyl group, C3-10 cycloalkenyl group, C 3 _i 0 cycloalkyl-Ci-6 alkyl group and non-aromatic heterocyclic group include those exemplified as the substituents that C3-10 cycloalkyl group and the like exemplified as the "hydrocarbon group" of the "hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • Examples of the substituent of the C6-14 aryl group, C 7 _i 3 aralkyl group, C 8 -i 3 arylalkenyl group and aromatic heterocyclic group include those exemplified as the substituents that C 6 -i4 aryl cycloalkyl group and the like exemplified as the
  • hydrocarbon group of the “hydrocarbon group optionally having substituent (s) " for R 1 , R 2 , R 3 or R x optionally have.
  • substituent (s) " formed by R 1 and R 2 in combination together with the adjacent nitrogen atom include those similar to the "nitrogen-containing heterocycle
  • Examples of the "5- to 7-membered nitrogen-containing heterocycle optionally having substituent (s) " formed by R 1 and R 3 in combination together with the adjacent nitrogen atom include a 5- to 7-membered nitrogen-containing heterocycle, from among the "nitrogen-containing heterocycle optionally having substituent (s) " formed by R A ' and R B ' in combination together with the adjacent nitrogen atom.
  • E is preferably a group represented by the formula
  • X is -S-, -0- or -NR X - (preferably -S-) ;
  • R x is a hydrocarbon group optionally having substituent (s) (preferably a Ci- 6 alkyl group (preferably methyl) ) ;
  • R 1 is a hydrogen atom, a hydrocarbon group optionally having substituent (s) or a heterocyclic group optionally having substituent (s) (preferably a hydrogen atom, a Ci_ 5 alkyl group optionally having substituent (s) , a C2-6 alkenyl group optionally having substituent (s) , a C2-6 alkynyl group optionally having substituent (s) , a C3-.10 cycloalkyl group optionally having substituent (s) , a C3-10 cycloalkyl-Ci-6 alkyl group optionally having substituent (s) , or a non-aromatic heterocyclic group optionally having substituent (s) ) ; and R 2 is a hydrogen atom; or
  • R 1 and R 2 in combination form, together with the adjacent nitrogen atom, a 4- to 7-membered nitrogen-containing heterocycle (preferably pyrrolidine, azetidine) optionally having substituent (s) .
  • a 4- to 7-membered nitrogen-containing heterocycle preferably pyrrolidine, azetidine
  • substituent (s) optionally having substituent (s) .
  • E is more preferably a group represented by the formula [0111]
  • X is -S-, -0- or -NR X - (preferably -S-) ;
  • R x is a Ci- 6 alkyl group (preferably methyl) ;
  • Ci-6 alkyl group preferably methyl, ethyl, propyl, isobutyl, isopentyl, neopentyl, 2-methylbutyl
  • a Ci-6 alkyl group optionally substituted by 1 to 5 substituents selected from
  • Ci_ 6 alkyl group (a) an amino group optionally mono- or di-substituted by Ci_ 6 alkyl group (s) (preferably methyl, ethyl) optionally
  • Ci-6 alkoxy group preferably methoxy, ethoxy
  • halogen atom preferably a fluorine atom
  • Ci- 6 alkoxy-carbonyl group preferably ethoxycarbonyl, tert-butoxycarbonyl
  • Ci-6 alkyl group preferably methyl, ethyl,
  • Ci_6 alkylsulfonyl group preferably methylsulfonyl
  • Ci-6 alkyl group preferably methyl
  • a Ci-6 alkyl group optionally substituted by 1 to 3 hydroxy groups
  • a 4- to 6-membered non-aromatic heterocyclylcarbonyl group preferably pyrrolidinylcarbonyl, piperazinylcarbonyl morpholinylcarbonyl ) optionally substituted by 1 to 3 substituents selected from
  • Ci-6 alkyl group preferably methyl
  • Ci-6 alkyl group preferably methyl
  • Ci-6 alkyl group preferably methyl

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Luminescent Compositions (AREA)

Abstract

La présente invention concerne un nouveau composé possédant une activité supérieure en tant que modulateur de l'ERR-α et utile en tant qu'agent pour la prophylaxie ou le traitement des maladies associées à l'ERR-α. La présente invention concerne un composé représenté par la formule (1) dans laquelle chaque symbole est tel que défini dans le mémoire, ou l'un de ses sels.
PCT/JP2012/070410 2011-08-04 2012-08-03 Composé hétérocyclique contenant de l'azote WO2013018929A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020228610A1 (fr) * 2019-05-10 2020-11-19 宁波鲲鹏生物科技有限公司 Dérivé polypeptidique et son procédé de préparation
RU2792236C1 (ru) * 2019-05-10 2023-03-21 Нингбо Кунпенг Биотекх Ко., Лтд. Производное полипептида и способ его получения

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20220030222A (ko) 2019-05-31 2022-03-10 이케나 온콜로지, 인코포레이티드 Tead 억제제 및 이의 용도
US11458149B1 (en) 2019-05-31 2022-10-04 Ikena Oncology, Inc. TEAD inhibitors and uses thereof

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH093067A (ja) 1995-06-16 1997-01-07 Hisamitsu Pharmaceut Co Inc 新規なピペリジン誘導体
WO1998033797A1 (fr) 1997-01-31 1998-08-06 Shionogi & Co., Ltd. Derives de pyrrolidine ayant une activite inhibant la phospholipase a2
WO2001014372A2 (fr) 1999-08-25 2001-03-01 Takeda Chemical Industries, Ltd. Agent promoteur de la production/secretion de neurotrophine
WO2001082925A1 (fr) 2000-04-28 2001-11-08 Takeda Chemical Industries, Ltd. Antagonistes de l'hormone concentrant la melanine
WO2001087834A1 (fr) 2000-05-16 2001-11-22 Takeda Chemical Industries, Ltd. Antagoniste de l'hormone de concentration de la melanine
US20020187953A1 (en) 2001-04-04 2002-12-12 Aubin Jane E. Estrogen receptor-related receptor alpha (ERRalpha) and cartilage formation
US20030152959A1 (en) 1997-02-27 2003-08-14 Mertz Janet E. Method of using estrogen-related receptor alpha (ERRalpha) status to determine prognosis, treatment strategy and predisposition to breast cancer, and method of using ERRalpha as a therapeutic target for the treatment of breast cancer
EP1602645A1 (fr) 2003-03-07 2005-12-07 Astellas Pharma Inc. Derive heterocyclique azote contenant du styryl 2,6-disubstitue
WO2006014325A2 (fr) 2004-07-02 2006-02-09 Exelixis, Inc. Modulateurs de c-met et leur methode d'utilisation
US20070191406A1 (en) 2006-02-15 2007-08-16 Roche Palo Alto Llc Heterocyclic antiviral compounds
WO2011016501A1 (fr) 2009-08-04 2011-02-10 武田薬品工業株式会社 Agent prophylactique ou thérapeutique pour le cancer

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002024695A2 (fr) 2000-09-22 2002-03-28 Ortho Mcneil Pharmaceutical, Inc. Octahydro-indolizine et quinolizine et hexahydro-pyrrolizine
EP1374233A1 (fr) 2001-03-28 2004-01-02 Bayer Chemicals AG Support de donnees optique contenant dans la couche d'informations un colorant triazacyanine en tant que compose photoabsorbant
JP2004525799A (ja) 2001-03-28 2004-08-26 バイエル アクチェンゲゼルシャフト 情報層中に吸光性化合物としてカチオン性アミノ複素環式色素を含有する光学データ記録媒体
US7135575B2 (en) * 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
WO2005072731A1 (fr) 2004-01-29 2005-08-11 X-Ceptor Therapeutics, Inc. Derives de 3-phenyl-n- ((1, 3, 4) thiadiazol-2-yl) -acrylamide et composes apparentes utiles comme modulateurs des recepteurs lies a l'oestrogene dans le traitement du cancer, de l'arthrite rhumatoide ou de troubles neurologiques
CA2573761A1 (fr) 2004-07-14 2006-02-23 Janssen Pharmaceutica N.V. Utilisation d'ethers aryliques modulateurs de recepteurs des oestrogenes
EP1805154A4 (fr) 2004-10-22 2009-11-25 Exelixis Inc Compositions pharmaceutiques
SI2132188T1 (sl) 2007-03-07 2012-04-30 Janssen Pharmaceutica Nv Substituiran fenoksi n-alkilirani tiazoldinedioni kot z estrogenom povezani receptor-alfa modulatorji
JP2010520308A (ja) 2007-03-07 2010-06-10 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ エストロゲン関連受容体−アルファモジュレーターとしての置換フェノキシアミノチアゾロン
UA98485C2 (ru) 2007-03-07 2012-05-25 Янссен Фармацевтика Н.В. ЗАМЕЩЕННЫЕ ФЕНОКСИТИАЗОЛИДИНДИОНЫ КАК МОДУЛЯТОРЫ α-РЕЦЕПТОРА ЭСТРОГЕНА
CL2008001914A1 (es) 2007-06-29 2009-07-17 Schering Corp Compuestos heterociclicos de nitrogeno y oxigeno,moduladores de gama secretasa, composicion farmaceutica de dichos compuestos; kit farmaceutico y su uso para prevenir o tratar enfermedades asociadas al sistema nervioso central como alzheimer, sindrome de down, enfermedades neurodegenerativas, inhibir el deposito de proteina amiloide.

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH093067A (ja) 1995-06-16 1997-01-07 Hisamitsu Pharmaceut Co Inc 新規なピペリジン誘導体
WO1998033797A1 (fr) 1997-01-31 1998-08-06 Shionogi & Co., Ltd. Derives de pyrrolidine ayant une activite inhibant la phospholipase a2
US20030152959A1 (en) 1997-02-27 2003-08-14 Mertz Janet E. Method of using estrogen-related receptor alpha (ERRalpha) status to determine prognosis, treatment strategy and predisposition to breast cancer, and method of using ERRalpha as a therapeutic target for the treatment of breast cancer
WO2001014372A2 (fr) 1999-08-25 2001-03-01 Takeda Chemical Industries, Ltd. Agent promoteur de la production/secretion de neurotrophine
WO2001082925A1 (fr) 2000-04-28 2001-11-08 Takeda Chemical Industries, Ltd. Antagonistes de l'hormone concentrant la melanine
WO2001087834A1 (fr) 2000-05-16 2001-11-22 Takeda Chemical Industries, Ltd. Antagoniste de l'hormone de concentration de la melanine
US20020187953A1 (en) 2001-04-04 2002-12-12 Aubin Jane E. Estrogen receptor-related receptor alpha (ERRalpha) and cartilage formation
EP1602645A1 (fr) 2003-03-07 2005-12-07 Astellas Pharma Inc. Derive heterocyclique azote contenant du styryl 2,6-disubstitue
WO2006014325A2 (fr) 2004-07-02 2006-02-09 Exelixis, Inc. Modulateurs de c-met et leur methode d'utilisation
US20070191406A1 (en) 2006-02-15 2007-08-16 Roche Palo Alto Llc Heterocyclic antiviral compounds
WO2011016501A1 (fr) 2009-08-04 2011-02-10 武田薬品工業株式会社 Agent prophylactique ou thérapeutique pour le cancer

Non-Patent Citations (22)

* Cited by examiner, † Cited by third party
Title
"Design of Molecules", vol. 7, 1990, HIROKAWA SHOTEN, article "IYAKUHIN no KAIHATSU", pages: 163 - 198
CANCER RESEARCH, vol. 68, 2008, pages 8805 - 12
CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 57, no. 12, 2009, pages 1415 - 1420
CHEMICAL & PHARMACEUTICAL BULLETIN, vol. 58, no. 8, 2010, pages 1123 - 1126
CIRCULATION, vol. 109, 2004, pages 433 - 8
EMBO J., vol. 16, 1999, pages 4270 - 9
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 44, 2009, pages 2038
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 44, 2009, pages 3272
J. BIOL. CHEM., vol. 271, 1996, pages 5795 - 804
J. CLIN. ENDOCRINOL. METAB., vol. 90, 2005, pages 3115 - 21
J. MED. CHEM., vol. 48, 2005, pages 7808 - 7820
JERRY MARCH: "Advanced Organic Chemistry"
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 57, 1935, pages 2627
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 81, 1959, pages 6498
JOURNAL OF THE CHEMICAL SOCIETY, 1954, pages 389
JOURNAL OF THE CHEMICAL SOCIETY, 1956, pages 1644
MOL. CANCER THER., vol. 8, 2009, pages 672 - 81
MOL. CELL ENDOCRINOL., vol. 172, 2001, pages 223 - 33
RICHARD C. LAROCK: "Comprehensive Organic Transformations"
THEODORA W. GREENE; PETER G. M. WUTS, PROTECTIVE GROUPS IN ORGANIC SYNTHESIS, pages 494 - 653
THEODORA W. GREENE; PETER G. M. WUTS: "Protective Groups in Organic Synthesis", pages: 404 - 4081
THEODORA W. GREENE; PETER G. M. WUTS: "Protective Groups in Organic Synthesis", pages: 494 - 653

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020228610A1 (fr) * 2019-05-10 2020-11-19 宁波鲲鹏生物科技有限公司 Dérivé polypeptidique et son procédé de préparation
RU2792236C1 (ru) * 2019-05-10 2023-03-21 Нингбо Кунпенг Биотекх Ко., Лтд. Производное полипептида и способ его получения
RU2792236C9 (ru) * 2019-05-10 2023-05-26 Нингбо Кунпенг Биотекх Ко., Лтд. Производное полипептида и способ его получения

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US8772277B2 (en) 2014-07-08

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